First-In-Human Phase I Study Of The Dna Repair Inhibitor Dt01 In Combination With Radiotherapy In Patients With In Transit Melanoma.

2555 Background: DT01 is a double stranded DNA oligonucleotide conjugated to cholesterol, which mimics false double strand breaks (DSB). DT01 triggers DNA repair proteins trapping, thereby inhibiting their repair activity. In non-clinical studies, DT01 showed antitumor activity as a single agent and in combination with radiotherapy (RT) in several tumor types including melanoma. No NOAEL could be defined. Methods: Subcutaneous peritumoral and intratumoral injections of DT01 were evaluated in combination with RT in a first-in-human phase I trial in patients (pts) with unresectable in-transit metastases of melanoma. Each pt received RT at a standard dose (3Gy/d 5 days/week for 2 weeks) on all selected tumor lesions, while only one or two tumor lesions were treated with DT01 3 times a week during both weeks of RT. A 3+3 dose escalation design was used. DT01 dose levels explored were 16, 32, 48, 64, and 96 mg. RT was given using a rectangular field by a linear accelerator. Tolerance was assessed using NCI C...